Composition of matter

ABSTRACT

The method relates to the field of asymmetric allylic amination and comprises preparing a chiral N-substituted allylic amine compound from the corresponding allylic substrates and substituted hydroxylamines, in the presence of a catalyst, said catalyst comprising copper compounds and a chiral ligand. Examples of chiral amine compounds which can be made using the method include Vigabatrin, Ezetimibe Terbinafine, Naftifine 3-methylmorphine, Sertraline, Cinacalcet, Mefloquine hydrochloride, and Rivastigmine. There are over 20,000 known bioactive molecules with chiral N-substituted allylic amine substructure. The method may also be used to produce non-natural chiral β-aminoacid esters, a sub-class of chiral N-substituted allylic amine compounds. Examples of β-aminoacid ester which can be produced by the disclosed method, include, but are not limited to, N-(2-methylpent-1-en-3-yl)benzenamine and Ethyl 2-methylene-3-(phenylamino)butanoate. Further, the products of the method described herein can be used to produce chiral heterocycles and bioactive molecules or materials. A novel chiral copper-BINAM nitrosoarene complex is also set forth.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a continuation-in-part (“CIP”) of U.S. patentapplication Ser. No. 14/418,540, entitled “METHOD OF PRODUCING CHIRALN-SUBSTITUTED ALLYLIC AMINE COMPOUNDS”, filed on Jan. 30, 2015, whichwas filed under 35 U.S.C. §371 and claims priority to the PCTApplication No. PCT/US2013/054011, filed on Aug. 7, 2013, which claimspriority to a provisional application, U.S. Application No. 61/680,551,which was filed on Aug. 7, 2012.

STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT

Not Applicable.

REFERENCE TO A “SEQUENCE LISTING,” A TABLE, OR A COMPUTER PROGRAM

Not Applicable.

DESCRIPTION OF THE DRAWINGS

The drawings constitute a part of this specification and includeexemplary embodiments of the method of producing chiral N-substitutedallylic amine compounds. It is to be understood that in some instances,various aspects of the invention may be shown exaggerated or enlarged tofacilitate an understanding of the invention. Therefore the drawings maynot be to scale. In addition, in the embodiments depicted herein, likereference numerals in the various drawings refer to identical or nearidentical structural elements.

FIG. 1 is a diagram of the method for producing chiral N-substitutedallylic amine compounds.

FIG. 2 is an X-Ray structure of the Cu-BINAM-nitroso complex.

DETAILED DESCRIPTION

The subject matter herein is described with specificity to meetstatutory requirements. However, the description itself is not intendedto necessarily limit the scope of claims. Rather, the claimed subjectmatter might be embodied in other ways to include different steps orcombinations of steps similar to the ones described in this document, inconjunction with other present or future technologies.

Many natural products, pharmaceutical compounds, and agrochemicalscontain chiral amine functionality. The antiepileptic drug Vigabatrin((R or S)-4-aminohex-5-enoic acid) and the cholesterol lowering drugEzetimibe((3R,4S)-1-(4-fluorophenyl)-3-[(3S)-3-(4-fluorophenyl)-3-hydroxypropyl]-4-(4-hydroxyphenyl)azetidin-2-one)are examples of two commercially useful chiral amine compounds that canbe produced by the described method. Terbinafine([(2E)-6,6-dimethylhept-2-en-4-yn-1-yl](methyl)(naphthalene-1-ylmethyl)amine)and Naftifine((2E)-N-methyl-N-(1-naphthylmethyl)-3-phenylprop-2-en-1-amine) areexamples of two commercially useful N-substituted allylic aminecompounds. Examples of commercially useful chiral amine based compoundsinclude 3-methylmorphine ((5α,6α)-7,8-didehydro-4,5-epoxy-3-methoxy-17-methylmorphinan-6-ol) (painrelief), Sertraline ((1S,4S)-4-(3,4-dichlorophenyl)-N-methyl-1,2,3,4-tetrahydronaphthalen-1-amine)(depression), Cinacalcet(R)—N-[1-(1-naphthyl)ethyl]-3-[3-(trifluoromethyl)phenyl]propan-1-amine(hyperparathyroidism), Mefloquine hydrochloride([(R,S)-2,8-bis(trifluoromethyl)quinolin-4-yl]-(2-piperidyl) methanol)(malaria), and Rivastigmine ((S)-3-[1-(dimethylamino)ethyl]phenylN-ethyl-N-methylcarbamate) (Alzheimers). There are over 20,000 knownbioactive molecules with chiral N-substituted allylic aminesubstructure. Current efforts in asymmetric allylic amination usepre-functionalized allylic substrates and Pd, Rh or Ir-based chiralcomplexes as catalysts. Additionally, chiral β-aminoacids have beenproduced using Aza Byalis-Hillman reactions utilizing N-protected iminesand α,β-unsaturated carbonyl compounds.

A method for producing chiral N-substituted allylic amine compounds isdescribed herein. The method comprises preparation of a chiralN-substituted allylic amine from the corresponding olefins andhydroxylamines, in the presence of a catalyst. The catalyst comprises acopper compound and a chiral ligand. The aminating agents aresubstituted hydroxylamines. The method may be used to producenon-natural chiral β-aminoacid esters, a sub-class of chiralN-substituted allylic amines. Further, the products of the methoddisclosed can be used to produce chiral heterocycles, and bioactivemolecules or materials.

The method comprises mixing an olefin compound containing allylic C—Hgroup, with an aminating reagent. The aminating reagent comprises asubstituted hydroxylamine. The method further comprises adding a chiralligand and a copper (Cu(I)) compound to the mixture. The active catalystis formed in situ by the reaction of the copper [Cu(I)] compound withthe chiral ligand. The reaction results in the production of a chiralallyl amine through asymmetric allylic amination. This is a nitroso-enereaction in which nitroso compounds are generated in situ via oxidationof hydroxylamines by the metal catalyst. The reaction results in verygood yields and high enantioselectivity rate.

Through the above described method, a variety of chiral allyl amines maybe produced. The antiepileptic drug Vigabatrin ((R orS)-4-aminohex-5-enoic acid) and the cholesterol lowering drug Ezetimibe((3R,4S)-1-(4-fluorophenyl)-3-[(3S)-3-(4-fluorophenyl)-3-hydroxypropyl]-4-(4-hydroxyphenyl)azetidin-2-one)are two non-limiting examples of two commercially useful chiral aminecompounds that can be produced by the described method. Terbinafine([(2E)-6,6-dimethylhept-2-en-4-yn-1-yl](methyl)(naphthalene-1-ylmethyl)amine)and Naftifine((2E)-N-methyl-N-(1-naphthylmethyl)-3-phenylprop-2-en-1-amine) areexamples of two commercially useful N-substituted allylic aminecompounds. Examples of commercially useful chiral amine based compoundsinclude 3-methylmorphine ((5α,6α)-7,8-didehydro-4,5-epoxy-3-methoxy-17-methylmorphinan-6-ol) (painrelief), Sertraline ((1S,4S)-4-(3,4-dichlorophenyl)-N-methyl-1,2,3,4-tetrahydronaphthalen-1-amine)(depression), Cinacalcet(R)—N41-(1-naphthyl)ethyl]-3-[3-(trifluoromethyl)phenyl]propan-1-amine(hyperparathyroidism), Mefloquine hydrochloride([(R,S)-2,8-bis(trifluoromethyl)quinolin-4-yl]-(2-piperidyl) methanol)(malaria), and Rivastigmine ((S)-3-[1-(dimethylamino)ethyl]phenylN-ethyl-N-methylcarbamate) (Alzheimers). There are over 20,000 knownbioactive molecules with chiral N-substituted allylic aminesubstructure. Additionally, the method may be used in the production ofnon-natural chiral β-aminoacid esters, a sub-class of chiralN-substituted allylic amines. Examples of chiral β-aminoacid esters thatcan be produced through the described method include, but are notlimited to, N-(2-methylpent-1-en-3-yl)benzenamine and Ethyl2-methylene-3-(phenylamino)butanoate). Further, chiral heterocycles, andbioactive molecules or materials can be produced from the products ofthe method disclosed herein. This method could be used in thepharmaceutical industry, the biotech industry, the agrochemicalindustry, the chemical industry, and the polymer industry, as well asany other industry where chiral amines are used.

Since many natural products, pharmaceutical compounds, and agrochemicalscontain chiral amine functionality, the transition metal catalyzedasymmetric amination of olefins has received significant importance inorganic synthesis. [You, S. et al., J. Am. Chem. Soc. 2001, 123, 7471;Hayashi, T. et al., Tetrahedron Lett. 1990, 31, 1743; Jorgensen, K. A.et al., Chem. Rev. 1998, 98, 1689; Evans, P. A. et al., J. Am. Chem.Soc. 1999, 121, 6761.] The direct and most efficient way to synthesizethese chiral amines involves the direct functionalization of allylic C—Hbonds via asymmetric allylic amination. Most efforts in asymmetricallylic amination use pre-functionalized allylic substrates, whichrequire more synthetic steps than the method described herein.Additionally, prior methods utilize expensive Pd, Rh or Ir-based chiralcomplexes as the common catalysts [US 20060199728 A1] for asymmetricallylic amination of pre-functionalized allylic substrates. [Trost, B.M. et al. Chem. Pharm. Bull. 2002, 50, 1-14; Chem. Rev. 2003, 103,2921-2943].

U.S. patent publication number US 2008/0194841 A1 and U.S. Pat. No.6,399,787 B1 disclose the preparation of optically active β-aminoacidsvia asymmetric hydrogenation reaction. Alternate methods of producingchiral β-aminoacids and related chiral heterocycles mainly involve AzaByalis-Hillman (ABH) reactions, which use N-protected imines andα,β-unsaturated carbonyl compounds. The major limitations of this ABHmethod include: i) the method is not useful for the preparation ofchiral N-aryl allyl amines; and ii) the method's reaction rates are verypoor. [Lamaty, F. et al., Chem. Rev. 2009, 109, 1-48].

US patent publication no. US 2008/0167312 A1 discloses the preparationof bioactive allyl amine Terbinafine and medical applications. US patentpublication no. US 2006/0199728 A1 discloses Ir-based catalysts withphosphoramidite ligands for asymmetric allylic amination andetherification of allylic acetates.

The method described herein provides a simple and direct method for theproduction of chiral allyl amines by using simple olefins andinexpensive metal catalyst for asymmetric allylic amination, using acopper catalytic system.

In the method described herein, one reagent comprises an olefincontaining allylic C—H group with the general structure R—C(C—HR¹)═CHR².The structure can be further represented as:

Useful olefins include, but are not limited to, the following examples:

Combinations of above olefins may also be implemented in the method ofinvention.

In the method described herein, one reagent comprises an aminatingreagent. The aminating reagents are substituted hydroxylamines Examplesof aminating reagents which can be used include, but are not limited to,aryl hydroxylamines, N-Boc hydroxyl amines, Phenyl hydroxylamine, Tolylhydroxylamine, 2-lodophenyl hydroxylamine, and N-Boc hydroxylamine. Thefollowing aryl and N-Boc hydroxylamines are non-limiting examples ofaminating reagents which may be used:

R(+)-BINAM may be used as the chiral ligand. The following chiralligands are non-limiting examples of chiral ligands which may beutilized in the described method:

Tetrakis(acetonitrile)copper(I) hexafluorophosphate, whose chemicalformula is [Cu(CH₃CN)₄]PF₆, may be used as the copper (Cu(I)) compound.

Examples and Results

All experiments were performed under nitrogen atmosphere.Dichloromethane (dry, 99.99+) from Alfa Aesar was used as purchased. Thefollowing olefins were used in experiments: 2-methyl-2-pentene,2-methyl-2-heptene, Ethyl tiglate, Methyl trans-2-methyl-2-pentenoate.All olefins, including tiglate esters, and N-Boc hydroxylamine werepurchased from Sigma Aldrich and used as purchased. Most of the ligandsand catalysts were purchased from Sigma-Aldrich and Strem chemicals,except octahydro R(+)-BINAM which was synthesized by the reduction ofR(+)-BINAM ligand as described in Kano, T.; Tanaka, Y.; Osawa, K.;Yurino, T.; Maruoka, K. J. Org. Chem. 2008, 73, 7387. Arylhydroxylamineswere synthesized by Zn-metal reduction of commercially availablenitroarenes, as described in Kamm, O. Org. Synth. Col. Vol. I, 1958, p.445.

IR spectra were recorded on JASCO 480-plus instrument. 1H and 13C NMRwere recorded on Varian 400 MHz NMR using CDCl₃ solvent, unlessotherwise noted. Products were confirmed by Agilent GC-MS (7890A-5975C).To measure enantiomeric excess, GC (HP Series II 5890) with chiralcapillary column (Restek betadex-30 m×0.25×0.25μ) and HPLC (Dionex,Ultimate 3000) with Chiralpak AS-H column (4.6×250 mm 5μ) were used.

General Procedure for Asymmetric Allylic Amination:

Under nitrogen atmosphere, the solution of precatalyst copper (Cu(I))compound Cu(CH₃CN)₄PF₆ (10 mg, 0.025 mmol) and ligand R(+)-BINAM (14 mg,0.05 mmol) in dichloromethane (3 mL) was stirred at room temperature forten (10) minutes. Then the olefin (1 mmol) was added followed by theslow addition of arylhydroxylamine (0.25 mmol) solution indichloromethane (5 mL) via syringe pump over five (5) hours at roomtemperature. Reactions were allowed to continue for two (2) more hoursto get complete consumption of arylhydroxylamine Once the productformation was confirmed by GC-MS, the mixture was filtered throughcelite and the filtrate was concentrated to dryness. The crude productwas purified by column chromatography (Hexane/Ethylacetate eluents) togive the corresponding allyl amine product, which was then directlyanalyzed by NMR and chiral HPLC or chiral GC to determine the purity andenantiomeric excess.

Example 1 N-(2-methylpent-1-en-3-yl)benzenamine

The solution of Cu(CH₃CN)₄PF₆ (10 mg, 0.025 mmol) and ligand R(+)-BINAM(14 mg, 0.05 mmol) in dichloromethane (3 mL) was stirred at roomtemperature for 10 minutes. To the same flask, addition of2-methyl-2-pentene (1 mmol, 122 μL) was followed by the slow addition ofphenylhydroxylamine (0.25 mmol, 27.5 mg) solution in dichloromethane (5mL) via syringe pump over 5 hours at room temperature. Reaction wasallowed to continue for two more hours to get complete consumption ofphenylhydroxylamine. Product was confirmed by GC-MS (M⁺=175.10) and NMRanalysis. Pure allylamine obtained in 68% yield with an optical purityof 69% ee. Chiral GC: t_(r)=35.00 min (major), t_(r)=35.42 min (minor).

Example 2 N-(2-methylpent-1-en-3-yl)benzenamine

All the procedure is same as in Example 1, except that S(−)-BINAM wasused in place of R(+)-BINAM. Pure allylamine obtained in 65% yield withan opposite enantioselectivity of 73% ee. Chiral GC: t_(r)=35.18 min(minor), t_(r)=35.58 min (major).

Example 3 N-(2-methylhept-1-en-3-yl)benzenamine

The solution of Cu(CH₃CN)₄PF₆ (10 mg, 0.025 mmol) and ligand R(+)-BINAM(14 mg, 0.05 mmol) in dichloromethane (3 mL) was stirred at roomtemperature for 10 minutes. To the same flask, addition of2-methyl-2-heptene (1 mmol, 155 μL) was followed by the slow addition ofN-phenylhydroxylamine (0.25 mmol, 27.5 mg) solution in dichloromethane(5 mL) via syringe pump over 5 hours at room temperature. Reaction wasallowed to continue for two more hours to get complete consumption ofN-phenylhydroxylamine. Product was confirmed by GC-MS (M⁺=203.10) andNMR analysis. Pure allylamine obtained in 64% yield with an opticalpurity of 67% ee. Chiral GC: t_(r)=41.65 min (major), t_(r)=41.88 min(minor).

Example 4 4-methyl-N-(2-methylpent-1-en-3-yl)benzenamine

The solution of Cu(CH₃CN)₄PF₆ (10 mg, 0.025 mmol) and ligand R(+)-BINAM(14 mg, 0.05 mmol) in dichloromethane (3 mL) was stirred at roomtemperature for 10 minutes. To the same flask, addition of2-methyl-2-pentene (1 mmol, 122 μL) was followed by the slow addition ofN-tolylhydroxylamine (0.25 mmol, 31 mg) solution in dichloromethane (5mL) via syringe pump over 5 hours at room temperature. Reaction wasallowed to continue for two more hours to get complete consumption ofN-tolylhydroxylamine Product was confirmed by GC-MS (M⁺=189.10) and NMRanalysis. Pure allylamine obtained in 62% yield with an optical purityof 74% ee. Chiral GC: t_(r)=38.56 min (major), t_(r)=39.07 min (minor).

Example 5 4-methyl-N-(2-methylhept-1-en-3-yl)benzenamine

The solution of Cu(CH₃CN)₄PF₆ (10 mg, 0.025 mmol) and ligand R(+)-BINAM(14 mg, 0.05 mmol) in dichloromethane (3 mL) was stirred at roomtemperature for 10 minutes. To the same flask, addition of2-methyl-2-heptene (1 mmol, 155 μL) was followed by the slow addition ofN-tolylhydroxylamine (0.25 mmol, 31 mg) solution in dichloromethane (5mL) via syringe pump over 5 hours at room temperature. Reaction wasallowed to continue for two more hours to get complete consumption ofN-tolylhydroxylamine Product was confirmed by GC-MS (M⁺=217.20) and NMRanalysis. Pure allylamine obtained in 59% yield with an optical purityof 66% ee. Chiral GC: t_(r)=44.98 min (major), t_(r)=45.28 min (minor).

Example 6 Ethyl 2-methylene-3-(phenylamino)butanoate

The solution of Cu(CH₃CN)₄PF₆ (10 mg, 0.025 mmol) and ligand R(+)-BINAM(14 mg, 0.05 mmol) in dichloromethane (3 mL) was stirred at roomtemperature for 10 minutes. To the same flask, addition of Ethyltiglate(0.75 mmol, 104 μL) was followed by the slow addition ofN-phenylhydroxylamine (0.25 mmol, 27.5 mg) solution in dichloromethane(5 mL) via syringe pump over 5 hours at room temperature. Reaction wasallowed to continue for two more hours to get complete consumption ofN-phenylhydroxylamine. Product was confirmed by GC-MS (M⁺=219.00) andNMR analysis. Pure allylamine obtained in 78% yield with an opticalpurity of 42% ee. Chiral HPLC: Chiralpak AS-H column usingHexanes/Ethanol/DEA (99:1:0.02) as mobilephase with a flow rate of 0.30mL/min; t_(r)=17.367 min (major), t_(r)=18.417 min (minor).

Example 7 Ethyl 3-(p-tolylamino)-2-methylenebutanoate

The solution of Cu(CH₃CN)₄PF₆ (10 mg, 0.025 mmol) and ligand R(+)-BINAM(14 mg, 0.05 mmol) in dichloromethane (3 mL) was stirred at roomtemperature for 10 minutes. To the same flask, addition of Ethyltiglate(0.75 mmol, 104 μL) was followed by the slow addition ofN-tolylhydroxylamine (0.25 mmol, 27.5 mg) solution in dichloromethane (5mL) via syringe pump over 5 hours at room temperature. Reaction wasallowed to continue for two more hours to get complete consumption ofN-tolylhydroxylamine. Product was confirmed by GC-MS (M⁺=232.90) and NMRanalysis. Pure allylamine obtained in 69% yield with an optical purityof 34% ee. Chiral HPLC: Chiralpak AS-H column using Hexanes/Ethanol/DEA(99:1:0.02) as mobile phase with a flow rate of 0.35 mL/min;t_(r)=14.108 min (minor), t_(r)=15.467 min (major).

Example 8 Methyl 2-methylene-3-(phenylamino)pentanoate

The solution of Cu(CH₃CN)₄PF₆ (10 mg, 0.025 mmol) and ligand R(+)-BINAM(14 mg, 0.05 mmol) in dichloromethane (3 mL) was stirred at roomtemperature for 10 minutes. To the same flask, addition of Methyltrans-2-methyl-2-pentenoate (0.75 mmol, 105 μL) was followed by the slowaddition of N-phenylhydroxylamine (0.25 mmol, 27.5 mg) solution indichloromethane (5 mL) via syringe pump over 5 hours at roomtemperature. Reaction was allowed to continue for two more hours to getcomplete consumption of N-phenylhydroxylamine. Product was confirmed byGC-MS (M⁺=219.10) and NMR analysis. Pure allylamine obtained in 73%yield with an optical purity of 33% ee. Chiral separation with NMR usingshift reagent (CDCl₃): δ 4.80 (major), δ 4.83 (minor).

New Matter

A novel catalytic intermediate has been synthesized and isolated that isrelevant to the asymmetric allylic amination procedure. This novelcatalytic intermediate, which comprises a chiral Cu-complex. It is achiral copper-BINAM nitrosoarene complex [Cu(BINAM)₂(ArNO)₂]OTf₂. OTf isa triflate functional group as would be recognized by one having skillin the art. X-Ray crystallographic analysis of [Cu(BINAM)2(ArNO)2]OTf2confirms the coordination of two BINAM ligands and two notrosoarenes(ArNO) to the Cu-metal. An ORTEP view of the X-Ray structure with atomicnumbering scheme of the Cu-BINAM-nitroso complex is set forth as FIG. 2.The previously reported and understood Cu-complexes exhibitscoordination through the nitrogen atom. However, the present compositionof matter does not share this common coordination; instead this novelCu-complex indicates the coordination of nitrosoarene through the Oxygenatom (O→Cu). This exhibits a staunch difference in the reactivity likelydue to the change in electron density at the metal center resulting fromthe BINAM ligands attached to it.

Structurally, the present complex is similar to copper-superoxocomplexes that generally exist as copper-monooxygenase enzymes. Yet,they are molecularly distinct. Most metal-nitroso complexes involve incoordination through the nitrogen-atom, instead of oxygen. However, thefact X-Ray crystallographic analysis has confirmed that the nitrosoarenemoiety of [Cu(BINAM)2(ArNO)2]OTf2 is coordinated through its oxygen atomis substantial. The catalytic implications of this metal complex willassist in the understanding of reaction mechanisms and selectivity,particularly in the asymmetric allylic amination procedure. Therefore,in addition to its clear uses in academic research, the complex has adirect use in both chemical and pharmaceutical industries such as forthe design and development of novel catalytic reactions. Likewise,because of the existing structural similarities, the current structurecan also be useful in predicting mechanistic pathways ofcopper-monooxygenase enzymes in biological systems.

An embodiment of a scheme for the synthesis [Cu(BINAM)2(ArNO)2]OTf2 isprovided below. A mixture of [Cu(OTf)₂] (0.635 g, 1.76 mmol) andR(+)-BINAM ligand (1.0 g, 3.52 mmol) was created. To this mixture, 10 mLtoluene was added. The mixture was stirred at room temperature for 6hours, after which the solvent was removed under vacuum and the crudeproduct which was directly re-crystallized from ethylacetate:hexanemixture (5:1) to obtain pure [Cu(BINAM)2]OTf2 complex (1.28 g, 78%yield).

In order to obtain crystals suitable for X-ray diffraction, theCu-complex (1.28 g, 1.37 mmol) obtained above was dissolved indichloromethane (10 mL) and N,N-diethyl-4-nitrosoaniline (0.40 g, 2.2mmol) was added. It is immediately noted that the dark brown solutionbecomes dark green. After stirring overnight (15 h), the dark greensolution was filtered, and the solvent was removed on rotavap. The solidresidue was triturated with diethyl ether (10 mL×2). Recrystallizationfrom CH2Cl2/haxane at −20° C. provided dark greenish crystals suitablefor X-ray diffraction.

For the purpose of understanding the original method of producing thecomposition of matter described herein, references are made in the textto exemplary embodiments of a method of producing or synthesizing thematter of composition, only some of which are described herein. Itshould be understood that no limitations on the scope of the inventionare intended by describing these exemplary methods. One of ordinaryskill in the art will readily appreciate that alternate but functionallyequivalent components, materials, designs, and equipment may be used.The inclusion of additional elements may be deemed readily apparent andobvious to one of ordinary skill in the art. Specific elements disclosedherein are not to be interpreted as limiting, but rather as a basis forthe claims and as a representative basis for teaching one of ordinaryskill in the art to employ the present invention.

Reference throughout this specification to features, advantages, orsimilar language does not imply that all of the features and advantagesthat may be realized should be or are in any single embodiment. Rather,language referring to the features and advantages is understood to meanthat a specific feature, advantage, or characteristic described inconnection with an embodiment is included in at least one embodiment.Thus, discussion of the features and advantages, and similar language,throughout this specification may, but do not necessarily, refer to thesame embodiment.

Reference throughout this specification to “one embodiment,” “anembodiment,” or similar language means that a particular feature,structure, or characteristic described in connection with the embodimentis included in at least one embodiment. Thus, appearances of the phrases“in one embodiment,” “in an embodiment,” and similar language throughoutthis specification may, but do not necessarily, all refer to the sameembodiment.

Moreover, the terms “substantially” or “approximately” as used hereinmay be applied to modify any quantitative representation that couldpermissibly vary without resulting in a change to the basic function towhich it is related.

All references to patents, documents, and other writings areincorporated by reference and their inclusion herein shall not beconstrued as an admission as to their status with respect to being ornot being prior art.

1. A chemical compound having the formula [Cu(BINAM)₂(ArNO)₂]OTf₂. 2.The chemical compound of claim 1 wherein the compound is a chiralcopper-BINAM nitrosoarene complex.
 3. A chemical compound comprising: a.a copper atom; b. two nitrosoarenes; c. two BINAM ligands; d. twotriflates.
 4. The chemical compound of claim 3 wherein the compound is achiral copper-BINAM-nitrosoarene complex.
 5. The chemical compound ofclaim 3 wherein the copper-nitroso complex is chiral.
 6. The chemicalcompound of claim 3 wherein at least one ligand is chiral.
 7. Thechemical compound synthesized from the process of combining coppertriflate (Cu(OTf)₂), and R(+)-BINAM in the presence of toluene.
 8. Thechemical compound of claim 7 wherein the process comprises the steps offirst creating a mixture of Cu(OTf)₂, R(+)-BINAM, and toluene, stirringthe mixture, and removing the solvent once a desired chemical compoundis produced.